Document Detail

Longitudinal neuroanatomical changes determined by deformation-based morphometry in a mouse model of Alzheimer's disease.
MedLine Citation:
PMID:  18547819     Owner:  NLM     Status:  MEDLINE    
Magnetic resonance imaging (MRI) of transgenic mice has the potential to provide valuable insight into the complex mechanisms underlying Alzheimer's disease (AD). Quantification of pathological changes is typically performed using manual segmentation methods, and requires a priori hypotheses about anatomical structures for volumetric measurement. Alternatively, deformation-based morphometry (DBM) has been shown to be a powerful, automated technique for detecting anatomical differences between populations by examining the deformation fields used to nonlinearly warp MR images. In this multiple timepoint, in vivo study, we have applied an automated, unbiased technique for the creation of a nonlinear, population-specific reference space from which robust DBM analysis can be performed. A general, linear mixed-effects model framework was developed to follow the evolution of structural changes in mouse brain from 2.5 to 9 months of age, and to examine neuroanatomical differences between a transgenic (TG) APP/PS1 murine model of AD and wild-type (WT) littermates. Morphometric abnormalities in the TG group were localized to regions of the hippocampus, cortex, olfactory bulbs, stria terminalis, brain stem, cerebellum, and ventricles. Although volumetric reductions were detected in TG mice, no general brain atrophy was found, suggesting a developmental, rather than a degenerative, pathological process. Finally, we established a strong correlation between a DBM summary measure and manually segmented volumes for each image in the dataset. These results support the utility of DBM to study longitudinal morphological changes in mouse models of central nervous system diseases in an automated and exploratory fashion.
Jonathan C Lau; Jason P Lerch; John G Sled; R Mark Henkelman; Alan C Evans; Barry J Bedell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-07
Journal Detail:
Title:  NeuroImage     Volume:  42     ISSN:  1095-9572     ISO Abbreviation:  Neuroimage     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-01     Completed Date:  2008-12-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215515     Medline TA:  Neuroimage     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19-27     Citation Subset:  IM    
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A2B4, Canada.
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MeSH Terms
Aging / pathology*
Alzheimer Disease / pathology*
Brain / pathology*
Computer Simulation
Disease Models, Animal*
Magnetic Resonance Imaging
Mice, Transgenic
Models, Anatomic*
Models, Neurological*

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